ABSTRACT
Objective To investigate the neuroprotective effect and its mechanism of therapeutic hypothermia induced by dihydrocapsaicin (DHC) on cerebral ischemia reperfusion injury in mice.Methods Twenty adult wild type (WT) mice were randomly divided into WT group and WT + DHC group,ten mice in each group.Twenty transient receptor potential receptor 1 (TRPV1) knockout mice were randomly divided into TRPV1 KO group and TRPV1 KO + DHC group,ten mice in each group.The model of focal cerebral ischemia reperfusion injury was established in all mice.The mice in the WT group and TRPV1 KO group were subcutaneously injected with physiological saline 1.25 mg · kg-1 · h-1 after reperfusion.The mice in the WT + DHC group and TRPV1 KO + DHC group were subcutaneously injected with DHC 1.25 mg · kg-1 · h-1 after reperfusion.All the mice were moved into the cage at 22 degrees centigrade after 90 minutes of reperfusion.The core body temperature during the reperfusion period was recorded in every 5 minutes to 24 hours after reperfusion.The neurobehavioral score was performed before anesthesia and 24 hours after anesthesia.After the neurobehavioral test,the brain tissue sections of mice were stained with 2,3,5-triphenyltetrazolium chloride;and the infarction rate of the brain tissue was calculated.Results There was no significant difference in the core body temperature among the four groups at 0,30 and 60 minutes after reperfusion (P ＞ 0.05).There was no significant difference in the core body temperature between 90 minutes and 0,30 and 60 minutes after reperfusion (P ＞ 0.05);but the core body temperature at 2,3,4,6,12 and 24 hours after reperfusion was significantly lower than that at 0,30,60 and 90 minutes after reperfusion in WT group,TRPV1 KO group and TRPV1 KO + DHC group(P ＜ 0.05).There was no significant difference in the core body temperature among the WT group,TRPV1 KO group and TRPV1 KO + DHC group at 2,3,4,6,12 and 24 hours after reperfusion (P ＞ 0.05).The core body temperature at 90 minutes and 2,3,4,6,12,24 hours after reperfusion was significantly lower than that at 0,30 and 60 minutes after reperfusion in WT + DHC group(P ＜ 0.05);and the core body temperature in WT + DHC group was significantly lower than that in WT group,TRPV1 KO group and TRPV1 KO + DHC group at the same time point(P ＜ 0.05).There was no significant difference in the total neurobehavioral score among the four groups before anesthesia (P ＞ 0.05).The total neurobehavioral score at 24 hours after reperfusion was significantly lower than that before anesthesia in the four groups (P ＜ 0.05).The total neurobehavioral score in WT + DHC group was significantly higher than that in WT group,TRPV1 KO group and TRPV1 KO + DHC group at 24 hours after reperfusion(P ＜0.05).There was no significant difference in the total neurobehavioral score among WT group,TRPV1 KO group and TRPV1 KO + DHC group at 24 hours after reperfusion (P ＞ 0.05).There was no significant difference in the score of spontaneous activity,climbing test,body proprioception and response to vibrissae touch among the four groups at 24 hours after reperfusion (P ＞ 0.05).The score of symmetry test of limbs movement and forepaw stretching test in WT + DHC group was significantly higher than that in WT group,TRPV1 KO group and TRPV1 KO + DHC group at 24 hours after reperfusion(P ＜ 0.05).There was no significant difference in the score of symmetry test of limbs movement and forepaw stretching test among the WT group,TRPV1 KO group and TRPV1 KO + DHC group at 24 hours after reperfusion (P ＞ 0.05).The infarction rate of brain tissue in WT + DHC group was significantly lower than that in the other three groups at 24 hours after reperfusion (P ＜ 0.05);but there was no significant difference in the infarction rate of brain tissue among the WT group,TRPV1 KO group and TRPV1 KO + DHC group (P ＞ 0.05).Conclusion Subcutaneous injection of DHC after focal cerebral ischemia and repeffusion of mice can induce therapeutic hypothermia by activating TRPV1 receptor,and reduce brain tissue damage and improve neurological function.